tbuckley/cabot-search huggingface dataset:
Rare <i>APOE</i> Missense Variants—Can We Overcome <i>APOE</i> ε4 and Alzheimer Disease Risk?
Authors: Gil D. Rabinovici, Dena B. Dubal
Journal: JAMA Neurology (2022)

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Inpatient outcomes of blinatumomab use: A national inpatient sample analysis.
Authors: Veli Bakalov, Amy Tang, Alexander M Helfand, Pragnan Kancharla, Richard White, Ahmed Khattab, Mohammad Alhousani, Yazan Samhouri
Journal: Journal of Clinical Oncology (2022)

e19021 Background: Blinatumomab, a bispecific (CD3/CD19) T-cell engager, is indicated for the treatment of acute lymphoblastic leukemia (ALL). The initial portion of each cycle is administered in the inpatient setting for close monitoring for cytokine release syndrome and neurotoxicity. Real world data are lacking on the cost of hospitalization, length of stay (LOS), and mortality in inpatients treated with blinatumomab. The goal of this study was to analyze the clinical outcomes of inpatient blinatumomab administration utilizing a national database. Methods: The ICD-10 diagnosis and procedure codes were used to identify Blinatumomab admissions and related complications from the 2018 version of the Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP). Weighted analysis was used to calculate national estimates. Logistic regression analyses were used to examine predictors of hospital outcomes (in-hospital mortality, length of stay, and cost), with p &lt; 0.05 considered statistically significant. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results: A total of 228 patients received inpatient blinatumomab in this cohort. Median age was 46 years old (IQR 26.8, 63.0) and 59.2% were males, 50.4% were white, and 47.4% had private insurance. The majority of patients received care at an urban teaching (96.1%) or large hospital (76.3%). The most relevant inpatient complications during hospitalization included hypotension (7.5%), pneumonia (6.1%), sepsis (9.2%), seizure (2.2%), neutropenia (6.1%), thrombocytopenia (14.0), tumor lysis syndrome (3.9%), and acute kidney injury (9.6%). Median LOS was 9.0 days (IQR 3.0-16.2) and median hospitalization charge was $114,936 USD (IQR 51,984.2-240,557.5). On multivariate regression analysis, dialysis (OR 1.67, 95% CI 1.05-2.65), blood product transfusion (OR 1.5, 95% CI 1.14-1.97), sepsis (OR 2.63, 95% CI 1.86-3.73), neutropenia (OR 1.86, 95% CI 1.23-2.81), and pancreatitis (OR 1.46, 95% CI 1.11-1.91) were all associated with longer LOS. Dialysis (OR 1.83, 95% CI 1.29-2.6), transfusions (OR 1.52, 95% CI 1.01-2.28), sepsis (OR 1.87, 95% CI 1.20-2.91) and neutropenia (OR 1.84, 95% 1.04-3.24) significantly increased the cost of hospitalization. Conclusions: In this cross-sectional study of a large national cohort of patients receiving inpatient blinatumomab, multiple blinatumomab associated toxicities led to increased LOS and cost of hospitalization.
Progression-free survival with subsequent anticancer therapies from a phase 3 trial of lorlatinib in treatment-naive patients (pts) with <i>ALK</i>+ advanced non–small cell lung cancer (NSCLC).
Authors: Benjamin J. Solomon, Todd Michael Bauer, Enriqueta Felip, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Konstantin K. Laktionov, Fiona Helen Blackhall, Elisa Dall’O, Anna Polli, Francesca Toffalorio, Tony S. K. Mok
Journal: Journal of Clinical Oncology (2022)

9069 Background: Lorlatinib, a brain-penetrant, third generation ALK tyrosine kinase inhibitor (TKI), demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs crizotinib in a phase 3 study in pts with previously untreated ALK+ advanced NSCLC (CROWN; NCT03052608). This study investigated the efficacy of treatments following progression on lorlatinib or crizotinib from the CROWN trial. Methods: Pts were randomized 1:1 to receive oral lorlatinib 100 mg daily or crizotinib 250 mg twice daily. The primary endpoint was PFS assessed per blinded independent central review, and secondary endpoints included time from randomization to the date of progression of disease on first subsequent systemic anticancer therapy or death (PFS2). Results: As of September 20, 2021, 91 of 149 patients (61.1%) vs 12 of 147 patients (8.2%) were still receiving lorlatinib vs crizotinib, respectively. In the lorlatinib arm, 33 of 149 patients (22.1%) received ≥1 subsequent systemic anticancer therapy vs 103 of 147 patients (70.1%) in the crizotinib arm. Among the patients who received subsequent systemic anticancer therapy, most patients in both treatment arms received ALK TKIs as first subsequent treatment: 63.6% and 93.2% in the lorlatinib and crizotinib arms. Chemotherapy was administered as first subsequent therapy to 36.3% and 2.9% of the patients, respectively. Median duration of treatment on first subsequent anticancer therapy was 9.6 months (IQR, 2.9-18.1 months) for lorlatinib arm and 13.3 months (IQR, 4.8-21.2 months) for crizotinib arm. Median PFS2 was not reached (NR; 95% CI, NR-NR) in the lorlatinib arm and was 39.6 months (95% CI, 27.4-NR) in the crizotinib arm, with a hazard ratio for lorlatinib vs crizotinib of 0.45 (95% CI, 0.30-0.67). Conclusions: While subsequent anticancer therapies offered clinical benefit in both treatment arms, PFS2 results indicated that clinical benefit was prolonged with lorlatinib vs crizotinib. Clinical trial information: NCT03052608.
Oncologic surveillance for variant histology upper tract urothelial carcinoma
Authors: A. Martini, M. De Angelis, C. Lonati, G. Fallara, L. Nocera, G. Basile, R. Leni, G. Rosiello, S. Scuderi, M. Bandini, G. Gandaglia, A. Mottrie, A. Gallina, F. Montorsi, A. Briganti, S. Shahrokh, M. Moschini
Journal: European Urology (2022)
Additional chemotherapy for EGFRm patients with the continued presence of plasma ctDNA EGFRm at week 3 after start of osimertinib first-line treatment (PACE).
Authors: Jan Alexander Stratmann, Fabian Acker, Lukas Aspacher, Juergen Alt, Friederike C Althoff, Sophie Heinzen, Nicola Gökbuget, Ina Müller, Lena Reiser, Sina Hehn, Hubert Serve, Martin Mänz, Frauke Meyer, Martin Sebastian
Journal: Journal of Clinical Oncology (2022)

TPS9157 Background: Epidermal growth factor receptor (EGFR) – mutated non-small cell lung cancer (NSCLC) is susceptible to EGFR targeting tyrosine kinase inhibitors (TKI), such as the third generation TKI osimertinib. However, response rate and duration vary between patients. Among others, the specific subtype of EGFR-mutation, its co-occurrence with other genetic alterations, and the detection of phosphorylated EGFR (pEGFR) in the plasma, and its clearance upon treatment were previously identified as markers that predict therapy response. A high proportion of patients with early (3-6 weeks after start) pEGFR clearance from plasma show impressive survival upon single-agent TKI. However, failure to achieve early clearance upon Osimertinib is associated with unfavorable outcome. For these patients, treatment concepts are lacking. Here, we report about the initiation of a clinical trial that evaluates the combination of EGFR-directed TKI and platinum-based chemotherapy as an early treatment escalation strategy for this high-risk patient population. Methods: PACE is a prospective multicenter single-arm investigator-initiated phase II trial. Patients with NSCLC harboring L858R or del19 EGFR mutation, who are treated with first-line Osimertinib are subjected to liquid biopsy-based early response assessment three weeks after start of therapy. Failure to clear pEGFR from plasma at this time point triggers treatment escalation with the addition of platinum-based doublet chemotherapy to the Osimertinib treatment. The primary outcome measure of the trial is progression-free survival (PFS), with the objective to assess the efficacy of biomarker-driven escalation of osimertinib therapy with a combination platinum-based regimen. Secondary outcome measures are the overall response rate (ORR), overall survival (OS), and the Quality of life (QLQ-C30, CTCAE-PROs) of the treated patients. In exploratory analyses, we will assess whether specific patterns of co-mutations are associated with early treatment failure (upon TKI) and pEGFR persistence. Fig. 1 illustrates the trial concept. A sample of 46 subjects achieves 80% power at a 0.05 significance level to detect a PFS of 14.4 months in the experimental treatment group when the PFS of the historic control group is 9.1 months; a total of 400 patients need to be screened within the national Network Genomic Medicine. Enrollment started in 12/2021. The clinical trial is supported by AstraZeneca and Guardant. EudraCT registration number: 2019-004757-88 .
Development of a novel nomogram to identify candidates for extended pelvic lymph-node dissection in prostate cancer using MRI and PSMA pet
Authors: D. Meijer, A.N. Vis, M.J. Roberts, A.R. Siriwardana, A. Morton, J.W. Yaxley, H. Samaratunga, L. Emmett, P.M. Van De Ven, M.W. Heijmans, H.G. Van Der Poel, M.L. Donswijk, T.N. Boellaard, I.G. Schoots, D.E. Oprea-Lager, G.D. Coughlin, P.J. Van Leeuwen
Journal: European Urology (2022)
Liver stiffness not fatty liver disease is associated with atrial fibrillation: The Rotterdam study
Authors: Laurens A van Kleef, Zuolin Lu, M Arfan Ikram, Natasja M S de Groot, Maryam Kavousi, Robert J de Knegt
Journal: Journal of Hepatology (2022)

Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear.Within the Rotterdam Study, a large prospective ongoing cohort, participants attending the abdominal ultrasound program between 2009-2014 were included. Exclusion criteria were no atrial fibrillation data or >20% missing data across analysis variables. Steatosis was assessed by ultrasound, liver stiffness by transient elastography and atrial fibrillation by 12-lead electrocardiograms. Incident atrial fibrillation was based on medical records and complete until 2014. Logistic and Cox-regression were used to quantify associations between fatty liver disease and atrial fibrillation.We included 5,825 participants (aged 69.5±9.1, 42.9% male), 35.7% had steatosis, liver stiffness measurement was available in 73.3%, and 7.0% had prevalent atrial fibrillation. Steatosis was not associated with prevalent atrial fibrillation in fully adjusted models (odds ratio [OR] 0.80; 95% CI 0.62-1.03), findings were consistent for non-alcoholic or metabolic dysfunction-associated fatty liver disease. Liver stiffness was significantly associated with prevalent atrial fibrillation (OR 1.09 per kPa, 95% CI 1.03-1.16); however, this was only persistent among those without steatosis (OR 1.18 per kPa, 95% CI 1.08-1.29). Lastly, no associations were found between steatosis (hazard ratio 0.88; 95% CI 0.59-1.33; follow-up 2.1 [1.1-3.2] years) and incident atrial fibrillation.Fatty liver disease was not associated with prevalent or incident atrial fibrillation, while liver stiffness was significantly associated with atrial fibrillation, especially among those without steatosis. This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation. We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease.NTR6831.There have been inconsistent reports about the potential links between fatty liver disease and atrial fibrillation (an irregular and often very fast heart rhythm). Herein, we show that liver stiffness (which is a marker of liver fibrosis), but not fatty liver disease, was associated with a higher prevalence of atrial fibrillation. We hypothesis that atrial fibrillation, rather than fibrosis, may be the cause of increased liver stiffness in participants without overt liver disease.
Treatment patterns and outcomes of patients with high-grade glioma during the COVID-19 pandemic.
Authors: Manik Chahal, Ghufran Abdulghaffar Aljawi, Rebecca A. Harrison, Alan Nichol, Brian Arthur Thiessen
Journal: Journal of Clinical Oncology (2022)

e14009 Background: During the first year of the COVID-19 pandemic there was global disruption in the provision of healthcare, causing significant pressure on hospital resources. High-grade gliomas (HGG) are rapidly progressive tumors, so patients with delays in diagnosis or treatment due to COVID-19-related disruptions might have poor outcomes. Therefore, we retrospectively evaluated the impact of the COVID-19 pandemic on treatment patterns and outcomes of patients with HGG in British Columbia (BC). Methods: A case cohort with a pathologic diagnosis of HGG (grade 4 astrocytoma and glioblastoma) treated at BC Cancer centers with radiotherapy between March 1, 2020 – March 1, 2021 (“COVID era”), and a control cohort treated between March 1, 2018 – March 1, 2019 (“pre-COVID era”) were identified. Patient demographics, tumor characteristics, treatment details, and dates of radiographic progression and death were included in the chart review. Analyses were performed with one-way ANOVA and Chi-squared tests for comparisons between eras. The Kaplan-Meier method was used to assess progression-free survival (PFS) and overall survival (OS) and differences in outcome between eras were investigated using the log-rank test. Results: 164 patients were identified: 85 in the pre-COVID era and 79 in the COVID era. There was no statistically significant baseline difference in age, sex, comorbidities, ECOG, tumor diameter, IDH mutation status, or MGMT methylation status between eras. There was also no statistically significant difference between time from symptom onset to first imaging, time from first imaging to surgery, time from surgery to oncologic consultation between eras, and time from surgery to radiotherapy. Significantly more patients were managed with biopsy relative to partial or gross total resection during the COVID era 22% (17/79) than the pre-COVID era 13% (11/85) (p = 0.04). However, radiation treatment (RT) did not differ between eras, with similar rates of conventionally fractionated RT in the pre-COVID era (87%, 74/85) and the COVID era (82%, 65/79) (p = 0.23). Use of concurrent and/or adjuvant temozolomide also was not significantly different between eras (p = 0.27 and p = 0.19, respectively). Median PFS was 7.0 months in both eras (CI 95 = 5.5 – 8.5 months for pre-COVID era, CI 95 = 5.8 – 8.2 months for COVID era, p = 0.3), and median OS was 13 months in the pre-COVID era (CI 95 = 10.3 – 15.7 months) and 16 months in the COVID era (CI 95 = 11.5 – 20.5 months), though this difference was not significant (p = 0.09). Conclusions: To our knowledge, this is the first study to assess outcomes of patients treated for HGG during the COVID-19 pandemic. We found that, despite less use of surgery in the COVID era, the outcomes of patients with HGG were not affected.
Hair Safe Study: Effects of scalp cooling on hair preservation and hair regrowth in breast cancer therapy—A prospective interventional study.
Authors: Christine Brunner, Ricarda Kofler, Daniel Egle, Verena Wieser, Magdalena Ritter, Samira Abdel Azim, Marlene Lehmann, Miriam Elisabeth Emmelheinz, Christian Marth
Journal: Journal of Clinical Oncology (2022)

12093 Background: Chemotherapy (CT) is a frequent and well established treatment in women with breast and gynecological tumors. Alopecia is one of the most common side effects of CT seriously impairing patient quality of life and body image. While other CT associated side effects can be controlled by supportive treatment strategy, adequate preventive measures for alopecia have been lacking. New evidence supports the efficacy of scalp cooling for alopecia prevention during CT. The aim of this study was to investigate preventive scalp cooling (SC) for chemotherapy-induced-alopecia in breast cancer patients undergoing standard adjuvant or palliative chemotherapy. We also analysed the impact of SC on hair regrowth after chemotherapy-induced-alopecia. Methods: This was a non-randomized, 2-arm interventional study conducted at the Department of Obstetrics and Gynecology, Medical University Innsbruck. Breast cancer patients receiving any chemotherapy associated with alopecia (i.e. taxane or anthracycline-based chemotherapy) were allocated either to an intervention group receiving SC or to a control group (no SC). SC during chemotherapy was applied by the Paxman scalp cooling system. The primary endpoint was hair preservation (HP) which was assessed by experts and patients using the CTCAE score and analysed during and after completion of chemotherapy. The secondary endpoint was hair regrowth (HR) after 3 and 6 to 9 months post chemotherapy. Results: The study population included 128 patients. The majority, namely 88 (69%) patients were assigned to the intervention group (CAP) and received SC, 40 patients were allocated to the control group (NCAP). HP was significantly higher in the group receiving SC than in the NCAP by patients’ self-evaluation (24% vs. 0%; P = 0.001) and experts’ assessment (72% vs. 0%, P ≤ 0.001). HR was comparable between both groups. Using the patients’ evaluation 50% of patients with taxane monotherapy had a grade 1 alopecia compared to 17% of patients with an anthracycline-taxane CT (50% vs 17%, P = 0.018). Drop-out rate was 13% in CAP and 5% in NCAP group. Main reasons for drop-out were hair loss and patients’ requests. Conclusions: Our study demonstrates that SCsignificantly reduced or avoided chemotherapy-induced-alopecia in breast cancer patients undergoing chemotherapy, especially in patients who received taxane-monotherapy. SC was a safe procedure without severe adverse events. Therefore, SC can be highly beneficial for patients receiving specific chemotherapy and the option should be made available to as many patients as possible. No significant effect was noted regarding regrowth after chemotherapy in the SC group.
Association of progression-free survival and overall response rate with overall survival in first-line randomized trials of immune checkpoint inhibitor–based regimens for metastatic non–small cell lung cancer (NSCLC): An FDA pooled analysis.
Authors: Bernardo Haddock Lobo Goulart, Sirisha Mushti, Somak Chatterjee, Erin A. Larkins, Martha Boeri Donoghue, Shenghui Tang, Richard Pazdur, Pallavi Shruti Mishra-Kalyani, Julia A. Beaver, Harpreet Singh
Journal: Journal of Clinical Oncology (2022)

9029 Background: Overall Survival (OS) has represented the endpoint of choice to support approvals of Immune Checkpoint Inhibitors (ICIs) in first-line metastatic NSCLC. Despite continued interest in the use of earlier clinical endpoints as true surrogates for OS in this setting, the correlation of Progression-Free Survival (PFS) and Overall Response Rate (ORR) with OS remain an area of active investigation. We conducted a patient-level and trial-level pooled analysis of first-line randomized trials of ICI-based regimens to assess correlations of early clinical endpoints of PFS and ORR with OS in first-line metastatic NSCLC. Methods: The analysis included randomized trials comparing ICI-based regimens (anti-PD-(L)1 with or without anti-CTLA4 antibodies, with or without platinum-based chemotherapy) to platinum-based chemotherapy alone for the first-line treatment of patients with metastatic NSCLC that were submitted to the U.S. Food and Drug Administration between July 2016 to March 2021 to support a marketing application. Patient-level associations were estimated using Spearman (rs) correlation coefficients for PFS and OS, and Cox Proportional Hazards models in RECIST response-based subgroups for ORR and OS. At the trial level, associations were estimated using R2 coefficients from weighted linear regression models, using the log of hazard-ratio (HRs) for PFS and OS and log-odds ratio for ORR. Results: The pooled analysis included 13 trials enrolling 9,285 patients total. Seven trials compared ICIs combined with chemotherapy vs chemotherapy; 6 trials compared ICIs alone vs chemotherapy. Among all patients, the distribution of PD-L1 expression was 31%, 66%, and 32% for PD-L1 &lt;1%, ≥1%, and ≥50%, respectively. The table shows the correlation coefficients for PFS and OS, and ORR and OS at the patient and trial levels. At the patient level, the OS HR comparing ICI-based regimens to chemotherapy was 0.54 (95% CI: 0.48, 0.61) for RECIST responders and 0.96 (95% CI: 0.90, 1.02) for non-responders. Conclusions: This pooled analysis did not indicate a strong correlation between endpoints of PFS and ORR with OS at the patient and trial levels in first-line randomized trials of ICI-based regimens for metastatic NSCLC, potentially because of use of subsequent therapies, cross-over to ICIs, and continuation of ICIs beyond progression. Future research will explore the correlation of alternative endpoints with OS, such as time to treatment discontinuation. Our analysis supports the continued importance of OS as an endpoint for first-line NSCLC trials of ICI-based regimens.[Table: see text]
Assessment of APOBEC3 expression as prognostic marker in squamous cell carcinoma of the penis
Authors: M.R. Hassler, B. Trimmel, C. Diemand, A. Oszwald, I. Ertl, U. Lemberger, A. Bruchbacher, R. Brettner, E. Compèrat, S.F. Shariat
Journal: European Urology (2022)